Psychosis, Schizo Affective Disorder, Schizophrenia, Schizophreniform
Conditions
Keywords
Early Psychosis, Levetiracetam
Brief summary
In order to establish target engagement and identify an effective dose the investigators will conduct a placebo-controlled single-dose parallel group trial of levetiracetam 185 mg and 500 mg in 24 medication-naïve early psychosis (EP) patients, measuring hippocampal activity by pulsed arterial spin labelling (ASL) pre-dose and 2 hours post-dose. The lower dose is calculated to achieve blood levels within the range that were associated with reduced hippocampal activity and improved cognition in patients with mild cognitive impairment; the higher dose is a typical antiepileptic dose. Successful demonstration of target engagement will be defined by an effect size of 0.5 or greater compared to placebo in reduction by levetiracetam of hippocampal blood flow measured by ASL. The optimal dose will be defined by maximal reduction of hippocampal perfusion in the absence of clinically-significant adverse effects. The investigators will also study 8 healthy control subjects to verify that baseline hippocampal blood flow is elevated in the sample of EP subjects.
Interventions
DRUGLevetiracetam
Levetiracetam is an atypical anticonvulsant that is frequently used in children and adults due to its superior tolerability, ease of use and excellent safety profile.
DRUGPlacebo
Prepared in capsules to appear identical to levetiracetam.
Sponsors
National Institutes of Health (NIH)
NYU Langone Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
16 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
1. Males and females 16 to 35 years of age, inclusive, at time of informed consent 2. Must have experienced a first episode of non-affective psychosis within 5 years and exhibit current psychosis, as defined by a score of ≥ 2 on one of the following psychosis items on the BPRS: conceptual disorganization, suspiciousness, hallucinations, unusual thought content, or grandiosity, for at least 4 days per week for at least 4 weeks 3. Must have a diagnosis of either schizophrenia, schizoaffective disorder or schizophreniform disorder as established by a Structured Clinical Interview for DSMIV TR (SCID) 4. Must not have taken an oral antipsychotic medication within the past 4 weeks prior to study enrollment or received a long acting injectable antipsychotic within 3 times the dosing interval 5. If female and of childbearing potential, patients must: 1. Have a negative urine pregnancy test (all females regardless of childbearing potential will be required to submit a pregnancy test) 2. Not be nursing or planning a pregnancy for the duration of the study through 30 days after the last dosing visit 3. Be abstinent or willing to use a reliable method of birth control from the screening visit and continue with the same method until termination from the study
Exclusion criteria
1. Current substance abuse or dependence for substances other than nicotine and THC (i.e., alcohol, amphetamines, barbiturates) 1. A positive urine toxic screen (excluding THC, tricyclic antidepressants, or benzodiazepines (if prescribed)) 2. Moderate or severe cannabis use disorder 3. Use of marijuana within the 72 hours prior to MRI scanning by self report 2. Diagnosis of major mood disorder or other Axis I disorder other than Schizophrenia, Schizoaffective Disorder or Schizophreniform Disorder 3. Current suicidal ideation. Suicidal ideation with intent or plan (indicated by affirmative answers to items 4 or 5 of the suicidal ideation section of the baseline C-SSRS) in the 6 months prior to screening or subjects who represent a significant risk of suicide in the opinion of the Principal Investigator and/or PhD or MD level clinician completing screening visit 4. Pregnant, nursing or positive urine pregnancy test 5. Significant medical or neurological illness by history or physical exam including seizure disorder, history of loss of consciousness related to head trauma or developmental disorder including mental retardation 6. Metal implants, pacemaker, or other metal in the body or medicinal patch 7. History of claustrophobia 8. Currently taking any antipsychotic medication (within 4 weeks)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Cerebral Blood Flow (CBF) | Baseline, 2 Hours Post-Treatment | CBF will be measured by Arterial Spin Labeling (ASL) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Levetiracetam 185 mg A single dose of 185mg of levetiracetam administered orally to participants. Participants undergo a 15-minute MRI scan using arterial spin labeling (ASL) before dosing and two hours post-dosing.
Levetiracetam: Levetiracetam is an atypical anticonvulsant that is frequently used in children and adults due to its superior tolerability, ease of use and excellent safety profile. | 8 |
| Levetiracetam 500mg A single dose of 500mg of levetiracetam administered orally to participants. Participants undergo a 15-minute MRI scan using arterial spin labeling (ASL) before dosing and two hours post-dosing.
Levetiracetam: Levetiracetam is an atypical anticonvulsant that is frequently used in children and adults due to its superior tolerability, ease of use and excellent safety profile. | 6 |
| Placebo A single dose of placebo administered orally to participants. Participants undergo a 15-minute MRI scan using arterial spin labeling (ASL) before dosing and two hours post-dosing.
Placebo: Prepared in capsules to appear identical to levetiracetam. | 7 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Did not meet entry criteria | 0 | 2 | 1 |
| Overall Study | Excluded due to motion in scanner | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Levetiracetam 185 mg | Total | Placebo | Levetiracetam 500mg |
|---|---|---|---|---|
| Age, Continuous | 25.13 years STANDARD_DEVIATION 5.94 | 25.16 years STANDARD_DEVIATION 4.49 | 25.17 years STANDARD_DEVIATION 2.35 | 25.17 years STANDARD_DEVIATION 4.07 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 6 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 15 Participants | 5 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 4 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 5 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 2 Participants | 9 Participants | 4 Participants | 3 Participants |
| Region of Enrollment United States | 8 participants | 21 participants | 7 participants | 6 participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 8 Participants | 19 Participants | 6 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 2 / 9 | 4 / 8 | 1 / 8 |
| serious Total, serious adverse events | 0 / 9 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Change in Cerebral Blood Flow (CBF)
CBF will be measured by Arterial Spin Labeling (ASL)
Time frame: Baseline, 2 Hours Post-Treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Levetiracetam 185 mg | Change in Cerebral Blood Flow (CBF) | -2.21 mL / (100g * min) | Standard Deviation 3.2 |
| Levetiracetam 500mg | Change in Cerebral Blood Flow (CBF) | -3.83 mL / (100g * min) | Standard Deviation 2.29 |
| Placebo | Change in Cerebral Blood Flow (CBF) | -1.29 mL / (100g * min) | Standard Deviation 1.66 |